Inhibition of nitric oxide (NO •) production in murine macrophages by flavones

Abstract

The effect of flavone (2-phenylbenzopyran-4-one) and three amino-substituted flavones on the production of nitrite by murine activated peritoneal macrophages was studied in vitro. Activated peritoneal macrophages obtained from mice pre-treated with concanavalin A (Con A) ( in vivo), after exposure in vitro to lipopolysaccharide (LPS) at a concentration of 100 ng/ml, produced nitrite (20.3 ± 2.5 nmol/10 6 cells), as measured after 24 hr by the Griess reaction. Stimulation of production of nitrite was inhibited by N G-mono-methyl-L-arginine, suggesting that nitrite was formed via nitric oxide (NO •) as a product of metabolism of arginine. Stimulation was inhibited by flavone and the aminoflavones (20–100 μM). 3′-amino-4′-hydroxyflavone was the most potent inhibitor of nitrite production. Genistein (5,7-dihydroxy-3-(4-hydroxy-phenyl)-4H-1-ben-zopyran-4-one) also inhibited production of nitrite, by a mechanism that appears not to involve protein tyrosine kinases. These results suggest that the flavones can modulate the immune responses and the inflammatory reactions by controlling production of nitric oxide.